Varespladib (LY315920) neutralises phospholipase A2 mediated prothrombinase-inhibition induced by Bitis snake venoms.

Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP
Nicholas J YoungmanBryan G Fry

Abstract

Anticoagulant toxicity is a common function of venoms produced by species within the Bitis genus. Potent inhibition of the prothrombinase complex is an identified mechanism of action for the dwarf species B. cornuta and B. xeropaga, along with some localities of B. atropos and B. caudalis. Snake venom phospholipase A2 toxins that inhibit the prothrombinase complex have been identified in snake venom, including an isolated phospholipase A2 toxin from B. caudalis. Current research is investigating the ability of the drug varespladib to inhibit snake venom phospholipase A2 toxins and reduce their toxicity. In particular, varespladib is being investigated as a treatment that could be administered prior to hospital referral which is a major necessity for species such as those from the genus Bitis, due to envenomations often occurring in remote regions of Africa where antivenom is unavailable. Using previously validated coagulation assays, this study aimed to determine if the toxins responsible for inhibition of the prothrombinase complex in the venom of four Bitis species are phospholipase A2 toxins, and if varespladib is able to neutralise this anticoagulant activity. Our results demonstrate that varespladib strongly neutralises th...Continue Reading

Citations

Jan 12, 2021·Neurotoxicity Research·Nicholas J YoungmanBryan G Fry
Nov 17, 2020·Toxicology Letters·Daniel DashevskyBryan G Fry
Apr 19, 2021·Biochimica Et Biophysica Acta. General Subjects·Guilherme H M SalvadorMarcos R M Fontes
Sep 28, 2021·Journal of Medicinal Chemistry·Upasana PuzariAshis K Mukherjee
Oct 31, 2020·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Nicholas J YoungmanBryan G Fry

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